Article

The role of neurotrophic factors, apoptosis-related proteins, and endogenous antioxidants in the differential temporal vulnerability of neonatal cerebellum to ethanol.

Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, USA.
Alcoholism Clinical and Experimental Research (impact factor: 3.34). 05/2003; 27(4):657-69. DOI:10.1097/01.ALC.0000060527.55252.71 pp.657-69
Source: PubMed

ABSTRACT Ethanol produces abnormalities in the developing nervous system, with certain regions being vulnerable during well-defined periods. Neonatal rodent cerebellum is particularly susceptible to ethanol during the early postnatal period [on postnatal days 4-5 (P4-5)], while this region is resistant to ethanol at a slightly later time (P7-9). We assessed basal levels of several substances which may be involved in differential temporal ethanol vulnerability in neonatal cerebellum, and analyzed alterations in these substances after early ethanol exposure.
Assessments were made of neurotrophic factors nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4; apoptosis-related proteins Bcl-2, Bcl-xl, Bax, Bcl-xs, Bad, phosphorylated-Bad, phosphorylated-Akt, and phosphorylated-c-Jun N-terminal kinase; and the antioxidants superoxide dismutase, glutathione reductase, and catalase. These analyses quantified basal levels (in controls), and sequential changes following acute ethanol exposure at the vulnerable and resistant cerebellar periods (P4, P7).
Comparisons of basal levels of the molecules assessed between P4 and P7 revealed higher levels of total proapoptotic Bad at p4, higher levels of the protective pAkt kinase at P7, and lower levels of proapoptotic pJNK at P7. Other basal levels did not differ. While ethanol-mediated alterations were found at both ages favoring both apoptosis and survival, the apoptosis-promoting changes produced on P4 exceeded those on P7, and most occurred within the first 2 hr after exposure, a critical survival/death period. The number of alterations favoring survival were similar at the two ages, but at P7 most occurred within the first 2 hr after exposure, possibly acting in a protective manner.
Differential temporal vulnerability to ethanol in the neonatal cerebellum appears to be paralleled by cellular alterations in neurotrophic factors, apoptosis-regulatory proteins, and/or antioxidant activities which generally favor apoptosis at the most sensitive age and survival at the resistant age.

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Keywords

acute ethanol exposure
 
analyzed alterations
 
antioxidants superoxide dismutase
 
apoptosis-promoting changes
 
apoptosis-regulatory proteins
 
apoptosis-related proteins Bcl-2
 
brain-derived neurotrophic factor
 
cellular alterations
 
critical survival/death period
 
differential temporal ethanol vulnerability
 
ethanol exposure
 
ethanol-mediated alterations
 
favor apoptosis
 
neurotrophic factors nerve growth factor
 
postnatal period [on postnatal days 4-5
 
resistant cerebellar periods
 
sequential changes
 
total proapoptotic Bad
 
two ages
 
well-defined periods